The aim of this project is to use metagenomics combined with metabolomics to identify causative pathogens and microbiome changes in clinical samples, to reduce antimicrobial resistance and to differentiate between the different causes of acute breathlessness (AB) to enable accurate personal treatment regimes.
This is an innovative and unique interdisciplinary project combining highly successful clinical, metagenomics, metabolomics, molecular microbiology, computational biology and diagnostics research. The project can involve both data analysis and laboratory-based research and can be flexible to the interests and expertise of the student.
AB is a common life-threatening feature of community acquired pneumonia, asthma and COPD exacerbations. It is known that these illnesses are complex and can include imbalance of the natural microbial community (microbiome) and infection by a variety of different organisms.
Understanding of the role of microbes in AB is very limited, but alterations within the microbiome, or growth of pathogens, are believed to cause COPD exacerbations. In community acquired pneumonia, the actual microbial agent is unidentified in 30-65% of cases. In both these illnesses identification of indicative microbiome changes or a causative agent, is crucial for optimal patient care and reducing antibiotic resistance.
The samples for this project come from the EMBER research programme (Ibrahim et al 2020) which has gathered full clinical data, including breath volatile organic compounds (VOCs), in addition to a series of clinical samples. Samples were obtained from patients with AB within 24 hours of acute admission. Metagenomics of the samples from these patients will identify infectious pathogens, and imbalance of the microbiome, whereas metabolomics will identify VOC signals associated with COPD and pneumonia. The novelty of this study is to compare these two different signals to increase understanding of respiratory disease.
Our preliminary analysis of metagenomic data from sputum samples from patients admitted with acute breathlessness identified potential causative infectious agents involved in the AB associated with COPD exacerbation and pneumonia. Comparison with healthy controls also showed decreased diversity of the microbiome in disease samples. Additionally, we have identified a VOC signature for pneumonia that requires further validation.
The cause and effect on patient treatment responses of these changes in the microbial community and the impact on the metabolome signal are not understood and need to be further investigated with greater computational analysis and complementary mechanistic studies, and is the aim of this project.
- Determine differences in microbial diversity associated with different causes of acute breathlessness.
- Identify infectious agents, virulence and antimicrobial genes associated with COPD or community acquired pneumonia.
- Determine the association between metagenomic and metabolomic signal and patient.
Expected outcomes and training:
This is a highly innovative and unique project based on clinical research of pneumonia, COPD and acute care, and microbial research on the interactions between the environment, bacteria and the host.
The student will be supervised by a clinical (Siddiqui, Greening) and non-clinical (Morrissey) and biostatistical/bioinformatics (Richardson) supervisory team and be well-provided with all the necessary training and facilities.
The student will have access to training in molecular microbiology, computational biology (e.g. bioinformatics) and clinical research. The student will also benefit from being part of large inter-disciplinary projects on air pollution and bacteria, and clinical research on COPD and asthma. Regular research meetings between the clinical and discovery science groups will greatly support the student.
Metagenomics combined with metabolomics will dramatically increase our understanding of how the microbiome and pathogens are involved in causing these acute respiratory diseases as well as inform on virulence factors and resistome. This project has the potential for high impact in diagnostics, clinical research, and molecular microbiology.
Ibrahim W, et al. Thorax 2021;0:1–8. doi:10.1136/thoraxjnl-2020-215667